Previous studies in dogs have demonstrated that heparin combined with myocardial ischemia (deprivation of oxygen supply to the heart muscle) can be a stimulus for growth of new blood vessels in the heart (collaterals). In a placebo controlled, double-blind study, we wished to examine the effects of ischemia and low molecular weight heparin therapy (Fragmin) in patients with myocardial ischemia during exercise, who had coronary artery disease. Patients were given subcutaneous Fragmin for one month and had repeat exercise training 3 times a day for 2 weeks. There were 10 patients treated with fragmin and 13 with placebo. 80% of the treated patients and 31% of the controls had improvement in rate pressure product during exercise after one month of treatment with Fragmin (p=0.055). Exercise duration to ischemia was also improved in all patients treated with Fragmin, but in only 62% of placebo treated patients. However, the magnitude of increase in the rate-pressure product (a measure of collateral growth) was not significantly different between the groups. Thus in this preliminary investigation, there is some evidence that combination of Fragmin and ischemia may be angiogenic (improves collateral growth) in patients with coronary artery disease. However, the results need to be confirmed by a large scale study.